​​The Cambridge Crystallographic Data Centre (CCDC).The CCDC websites use cookies. By continuing to browse the site you are agreeing to our use of cookies. For more details about cookies and how to manage them, see our cookie policy.

BlogScience Stories

​One of the most exciting events we hold at the CCDC are our blind tests of crystal structure prediction (CSP) methods. This one turned out to be the best yet. CSP is a really attractive problem as the challenge is beautifully simply to express, but monumentally difficult to solve. Perhaps this is why the entire CSP community comes together every few years, often pooling resources, to have a crack. It’s a wonderful model that could be applied to all sorts of challenges in chemistry and other areas of science.

After more than 40 years, the long C-C bond in 5-cyano-1,3-didehydroadamantane (CTCDEC) has been re-determined. The long bond between the bridgehead carbon atoms in the cyclopropane ring was originally reported in the paper by C.S.Gibbons and J.Trotter.[1] At 1.643(4) Å in length, it has been used as an example of a long C-C bond and is highlighted here by the yellow spheres.

​I recently came across a report about the largest known aromatic molecule, to date,1 and it got me thinking about similar entries in the CSD. I know from editing structures into the database that a significant proportion of new entries contain an aromatic system. The structures also seem to be getting bigger and bigger but I had never really connected these two features in any detail. First of all, I was delighted to learn that the supersized structures from the report were already in the CSD. Our new automated systems could deal with them without a problem and one of my colleagues had already cast their expert eye over them. In the report Dongho Kim and co-workers synthesised a [50]dodecaphyrin (KUHHIG, see below), the full name of which is in our curated entry but would have taken up half this blog so I decided not to include it! If you are wondering how to make your own supersized aromatic then the structure was synthesised to contain Hückel aromaticity by oxidising a non-aromatic [52]dodecaphyrin with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Dongho Kim and co-workers appear to be record breakers in the world of these structures; the largest known aromatic prior to this was a [46]decaphyrin palladium(II) complex (DONZEN), also synthesised by the same research groups.2

​I recently found a blog post from regular Chemistry World contributor Derek Lowe, highlighting an Early View Angewandte Chemie communication (doi: 10.1002/anie.201406886) in which the authors determined the crystal structures of two new polymorphs of the amino acid L-Phenylalanine. The paper also helps to clarify the relationship between several other Phenylalanine structures published over the last 20 years. Although Derek was surprised that determining the structure of a seemingly simple molecule had proved such a challenge for small-molecule crystallography, this type of challenge is not unusual. A notable example is the case of the two polymorphs of D-Ribose which evaded full determination for over 50 years (see ZZZFEE in the CSD from 1956!) until Jack Dunitz and co-workers published an article triumphantly exclaiming “The Crystal Structure of D-Ribose—At Last!” in 2010 (doi: 10.1002/anie.201001266).

The challenges involved in obtaining good quality single crystals to determine a structure should not be underestimated. Prior to the findings of this latest paper, the Cambridge Structural Database (CSD) contained five determinations of the structure of L-Phenylalanine (QQQAUJ-QQQAUJ04), from four different groups of researchers, all proposing different polymorphic forms based on the crystal structure data that they obtained.

As announced in our DOI press release we are delighted to be now assigning Digital Object Identifier (DOIs) to datasets of crystal structures deposited with CCDC. You may be familiar with the use of DOIs alongside article citations. These provide a persistent link that is guaranteed to take you to a page that provides metadata associated with an article and invariably a link to the article itself. Assigning an identifier such as a DOI reflects a desire for published content to be easily discoverable for the long term. CCDC believes that just as articles are worthy of citation, so too are the datasets that represent the primary output of the crystallographic community. We are not alone in this view as is evidenced by the Joint Declaration of Data Citation Principles (http://www.force11.org/datacitation) to which CCDC fully subscribes. These principles recognise the importance of data as a citable product of research for which credit and attribution is due. They also highlight attributes such as unique identification, access, persistence, versioning and interoperability which assigning DOIs can help facilitate.

​The European Crystallographic Meeting (ECM-28) at Warwick University in August this year marked my personal return to the world of crystallographic conferences after a gap of some eleven years. I recently returned to work at the CCDC, having left in 2002, and spent the intervening 11 years working in the drug discovery software industry which, although related and relevant, is quite a different community.

ECM events take place every year, except for those in which there is an IUCr Congress. Hence the last event took place in 2012 in Bergen, Norway, and it is some considerable time since the UK hosted an ECM, in 1977. The last major international crystallographic event in the UK took place in 1999, when the IUCr Congress was hosted in Glasgow – I had the honour of being on the organising committee on that occasion, and I’m delighted to say that the professional organisers for the Warwick ECM were the same people as at Glasgow – Northern Networking, run by Gill Moore. It was great to see her again after all this time.

It seems compulsory at the moment for every blog to mention the death of former British Prime Minister, Baroness Thatcher. Most reports focus on the life and political legacy of Britain’s only female Prime Minister, but of course prior to her life in politics, Thatcher began her career as a chemist.

As an undergraduate at The University of Oxford, the young Thatcher (then Margaret Roberts) undertook a fourth-year dissertation, in 1946-47, on X-ray crystallography of the antibiotic Gramicidin S. This work was carried out in the research group of Dorothy Hodgkin. Jon Agar gives a super account of the importance of science in shaping her life entitled "Thatcher, Scientist", in an article for Notes and Records of the Royal Society (doi:10.1098/rsnr.2010.0096)

Research into antibiotics was extremely important at the time, with Hodgkin determining the structure of penicillin in 1945. Thatcher never published a paper on the structure of Gramicidin, a sign perhaps of the challenging nature of the task. Thatcher herself said in a speech to the merging Chemical Society and The Royal Institute of Chemistry, on becoming an Honorary Fellow in 1979:

“In my day with her we were working on a molecule called gramicidin S. We thought it was the simplest nuclear protein but it turned out to be one of the most complicated and the structure took 30 years to get out. She did it, I didn't!”

We are pleased to announce that a recently published scientific communication involving researchers at the Pfizer Institute of Pharmaceutical Materials Science and CCDC has appeared as a CrystEngComm hot-article. The article summarises exciting results assessing the potential of the Mercury Solid Form Suite’s hydrogen bond propensity tool in screening potential co-crystal formers, and is available to view free of charge for 4 weeks from 20th March.

The published study describes the co-crystal screening of the anti-malarial drug pyrimethamine with various pharmaceutically acceptable adducts. Co-crystals offer completely new physical properties compared to a pure active ingredient and are viewed as a rich source of novel solid forms in the pursuit of a stable candidate for drug or agrochemical product development. Co-crystallising pairs of actives with different or complementary pharmacological effects is also an elegant potential route to multi-drug therapy. Developing methods to better suggest successful co-crystallisation experiments is, therefore, of great interest.

We at CCDC are keen advocates of the use of 3D structure to aid with the teaching of key chemical concepts. Following a demo of WebCSD and existing teaching material intended for undergraduate teaching, Dr Peter Hoare at the University of Newcastle has been developing (with the help of A level and masters students) bite-size worksheets intended for A Level standard chemistry, making use of our free teaching subset and WebCSD. Here, Peter's current MChem student Steve Carman explains a bit more about the exercises they have developed and how you can get your hands on them!

How important is solubility? Well, if like me you enjoy a sugar in your coffee, the answer is “pretty important”. In order for the sugar to be able to reach my taste-buds in adequate concentration to achieve that welcome sensation of sweetness, the sugar needs to be soluble enough in hot milky water. So too, for a successful drug, which, like the sugar, must dissolve and then reach a site of action in sufficient quantity to elicit a pharmacological response. Solubility is taken very seriously by pharmaceutical scientists.